Drug Interactions between Belviq and Permitil

MONITOR: Lorcaserin is a serotonergic drug. Potentially life-threatening neuroleptic malignant syndrome (NMS)-like reactions have been reported during use of serotonergic drugs and antipsychotics or other dopamine antagonists. The safety of lorcaserin when coadministered with antidopaminergic agents has not been systematically evaluated and has not been established.

MONITOR: Lorcaserin can cause elevations in prolactin, which may be additive to the hyperprolactinemic effects of dopamine antagonists. In clinical trials of at least one year duration, elevations of prolactin greater than the upper limit of normal, two times the upper limit of normal, and five times the upper limit of normal occurred in 6.7%, 1.7%, and 0.1% of lorcaserin-treated patients, compared to 4.8%, 0.8%, and 0.0% of placebo-treated patients, respectively. One patient treated with lorcaserin developed a prolactinoma. Although elevated serum prolactin levels have been associated with reports of amenorrhea, galactorrhea, gynecomastia and impotence, the clinical significance of hyperprolactinemia is unknown for most patients. Long-standing hyperprolactinemia may lead to low levels of estrogen and increased risk of osteoporosis. In rodents, an increase in mammary neoplasms has been found after chronic administration of prolactin-stimulating neuroleptic drugs. However, clinical and epidemiologic studies conducted to date have not established a causal relationship.

MONITOR: Coadministration with lorcaserin may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 2D6, including many neuroleptic agents and phenothiazines. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by lorcaserin. In a study consisting of 21 CYP450 2D6 extensive metabolizers, administration of the probe substrate dextromethorphan in combination with lorcaserin 10 mg twice daily for 4 days increased dextromethorphan peak concentrations (Cmax) by approximately 76% and systemic exposure (AUC) by approximately 2-fold. A dosage adjustment may be necessary for CYP450 2D6 substrates following the initiation or discontinuation of lorcaserin.

MANAGEMENT: Caution is advised when lorcaserin is prescribed in combination with antipsychotics or other antidopaminergic agents (e.g., droperidol, domperidone, metoclopramide, phenothiazines, tetrabenazine). Clinicians, caregivers, and family members should be apprised of the risk of neuroleptic malignant syndrome and be alert to potential signs and symptoms such as mental status changes (e.g., mutism, catatonia, stupor, coma, agitation, confusion, hallucinations, delusions), autonomic instability, restlessness, rigidity, ataxia, myoclonus, hyperreflexia, tremors, diaphoresis, elevated creatine phosphokinase levels, and hyperpyrexia. If NMS is suspected, treatment with these agents should be discontinued immediately and emergency medical attention sought. Prolactin levels should be measured when there are signs and symptoms of prolactin excess such as galactorrhea or gynecomastia. Consideration should be given to discontinuation of prolactin-stimulating drugs including lorcaserin.

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